title: Factors that affect accuracy of α-fetoprotein test in detection of hepatocellular carcinoma in patients with cirrhosis.
abstract: OBJECTIVE
  Measurements of α-fetoprotein (AFP) detect hepatocellular carcinoma (HCC) with low levels of sensitivity and specificity, and therefore are not recommended for use in liver cancer surveillance. However, AFP levels might accurately detect HCC in subgroups of patients. We performed a retrospective case-control study to identify features of patients with cirrhosis in whom levels of AFP correlated with HCC.
  
  
  METHODS
  We collected data from patients with cirrhosis, with (n = 452) or without (n = 676) HCC, diagnosed at Parkland Hospital in Dallas, Texas, from January 2005 through June 2012. We determined sensitivities and specificities with which different levels of AFP identified those with HCC; multivariate logistic regression was used to associate accurate identification of HCC with patient features (age, sex, race/ethnicity, alcohol intake, smoking, etiology of cirrhosis, presence of decompensation, and laboratory test results). We assessed the overall accuracy of these factors in detecting HCC using receiver operator characteristic curve analysis and the Delong method. We calculated levels of AFP that detect HCC with the highest levels of sensitivity and specificity in subgroups using receiver operator characteristic analysis.
  
  
  RESULTS
  The most common etiologies of cirrhosis were hepatitis C virus (HCV) infection (60%) and alcohol induced (22%). Nearly 11% of patients were human immunodeficiency virus (HIV)-positive. Levels of AFP greater than 20 ng/mL detected HCC with 70.1% sensitivity and 89.8% specificity. This AFP level identified patients with HCC with a c-statistic of 0.87 (95% confidence interval, 0.85-0.89); it was significantly more accurate in HCV-negative patients than in HCV-positive patients (c-statistic, 0.89 vs 0.83; P = .007). AFP levels of 59 ng/mL or greater most accurately detected HCC in patients with HCV-associated cirrhosis; levels of AFP of 11 ng/mL or greater accurately identified HCC in HCV-negative patients. The level of AFP identified early stage HCC with a c-statistic of 0.62 (95% confidence interval, 0.58-0.66), and had a significantly higher level of accuracy for HIV-positive patients than for HIV-negative patients (c-statistic, 0.81 vs 0.59; P < .001).
  
  
  CONCLUSIONS
  Based on a retrospective analysis of data from patients with cirrhosis, with or without HCC, AFP level most accurately detects HCC in patients without HCV infection. It detects HCC with a high level of accuracy in patients with cirrhosis and HIV infection.
authors.affiliation: Department of Pathology, University of Texas Southwestern Medical Center, Dallas, Texas.
authors.forename: Purva
authors.initials: P
authors.lastname: Gopal
authors.affiliation: Department of Surgery, University of Texas Southwestern Medical Center, Dallas, Texas; Harold C Simmons Cancer Center, University of Texas Southwestern Medical Center, Dallas, Texas.
authors.forename: Adam C
authors.initials: AC
authors.lastname: Yopp
authors.affiliation: Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan; Center for Clinical Management Research, Ann Arbor Veterans Affairs Healthcare Systems, Ann Arbor, Michigan.
authors.forename: Akbar K
authors.initials: AK
authors.lastname: Waljee
authors.affiliation: Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, Texas.
authors.forename: Jason
authors.initials: J
authors.lastname: Chiang
authors.affiliation: Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, Texas.
authors.forename: Mahendra
authors.initials: M
authors.lastname: Nehra
authors.affiliation: Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, Texas.
authors.forename: Pragathi
authors.initials: P
authors.lastname: Kandunoori
authors.affiliation: Harold C Simmons Cancer Center, University of Texas Southwestern Medical Center, Dallas, Texas; Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, Texas; Department of Clinical Sciences, University of Texas Southwestern Medical Center, Dallas, Texas. Electronic address: amit.singal@utsouthwestern.edu.
authors.forename: Amit G
authors.initials: AG
authors.lastname: Singal
mesh_terms: D015415:Biomarkers / Q000097:blood*; D006528:Carcinoma, Hepatocellular / Q000175:diagnosis*; D016022:Case-Control Studies; D005260:Female; D006801:Humans; D008103:Liver Cirrhosis / Q000150:complications*; D008113:Liver Neoplasms / Q000175:diagnosis*; D008297:Male; D008875:Middle Aged; D012189:Retrospective Studies; D012680:Sensitivity and Specificity; D013781:Texas; D000509:alpha-Fetoproteins / Q000032:analysis*
chemical_list: D015415:Biomarkers; D000509:alpha-Fetoproteins
keywords: AIDS; Biomarkers; Liver Disease; Screening